ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.487G>A (p.Gly163Arg) (rs281865128)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538322 SCV000636250 pathogenic Charcot-Marie-Tooth disease, type I 2019-12-01 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 163 of the MPZ protein (p.Gly163Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Charcot-Marie-Tooth type 1 (CMT1) (PMID: 8800924) as well as in three members of a family affected with CMT1 (PMID: 27088055). ClinVar contains an entry for this variant (Variation ID: 208148). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). A different variant (c.487G>C) giving rise to the same protein effect observed here (p.Gly163Arg) has been reported to segregate with disease in two families affected with CMT1 (PMID: 12207932, 15170620), indicating that this residue may be critical for protein function. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000193606 SCV000243905 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2015-03-26 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000789471 SCV000928827 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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